One of the most challenging tasks facing those in the fields of dentistry and orthopedic medicine has been the architectural reconstruction of osseous defects which may have been a sequela of infection induced bony/sequestration, developmental malformation, surgical resection, or traumatic avulsion. The need to initiate repair and to restore structurally deficient bone has prompted the development and application of a wide assortment of materials.
The biodegradable synthetic polymers, specifically, copolymers of polylactic (PLA) and polyglycolic acid (PGA), appear to satisfy many of the requirements necessary to replace autogenous cancellous marrow as the grafting material of choice for maxillofacial defects. This material has the advantages of being otainable in large amounts and possessing a long shelf-life. Additionally, the use of this material (1) eliminates the need for a second surgical procedure in the host; (2) elicits minimal tissue reaction; (3) predictably biodegrades without forming toxic metabolites; (4) has the ability to act as a trestle for bony ingrowth; and (5) and may also possess osteogenic potential. Applicant has discovered that a combination of polylactic and polyglycolic acid copolymers and decalcified freeze-dried bone are able to produce a synergistic response with respect to osseous healing. This results in the accelerated osseous regeneration and a subsequent reduction in the amount of morbidity associated with maxillofacial avulsive injuries.
Maxillofacial injuries sustained in a combat environment account for a significant portion of combat-related injuries. It has been reported by Tinder et al. in "Maxillofacial Injuries sustained in the Vietnam Conflict", Military Medicine, Vol. 134, pages 668-672, 1969 that:
(1) During the Vietnam conflict for the year ending June 30, 1968, approximately 8.6-11.1% of U.S. Army patients admitted for trauma sustained injuries to the maxillofacial region;
(2) In patients whose injuries involved concomitant facial bone fractures, the mandible was the most frequently fractured bone; and
(3) In patients with mandibular injuries, 54% sustained avulsions of a significant portion of the mandible.
In the U.S. Navy Maxillofacial Casualty Study of patients with maxillofacial injury, reported by in 1980 by J. E. Kelly in Management of War Injuries to the Jaws and Related Structures, bone grafts for cases of avulsive osseous injury were required approximately 45% of the time. The mandible was again found to be the most frequently fractured facial bone with 86% of mandibular grafts being performed unilaterally.
In view of the findings that large percentage of maxillofacial injuries were unilateral mandibular avulsive wounds, much of the effort in maxillofacial graft or implant research has been directed towards using the mandible as the prototype to asess maxillofacial healing.
There is unanimity of opinion at the present time that for grafting large mandibular defects, autogenous bone is the preferred grafting material with the ileum the most desirable donor site. Complications involved with iliac crest donor procedures include an estimated blood loss of from 200-400 cc along with infrequent occurrences of adynamic ileus and herniation. Although the ileum provides a suitable supply of hematopoietic cancellous marrow, there are instances when contour and adaptability are better obtained through the use of rib grafts (i.e. restoration of the curvature of the mandibular symphysis). Harvesting of ribs is additionally associated with a 25-35% incidence of pneumothorax.
While small defects of 1 cm or less may be corrected by the use of sliding bone grafts, larger discontinuity grafts may require the use of metal trays to contain the graft. Perforation of the tray through mucosa may require a second surgical procedure for removal or to control infection. In addition, in long span cases, there is a tendency for inadequate osseous proliferation especially in the middle of the graft. The above morbidity translates into an 84% success rate for grafting mandibular discontinuity defects with autografts.
In light of the preceeding discussion concerning methods of mandibular grafting, alternative methods have been sought in the form of alloimplants and allografts. The morbidity associated with autograft procedures makes the search for an alloimplant or allograft even more prudent. The biodegradable synthetic polymers have been investigated as osseous alloimplants due to the following characteristics:
(1) adequate initial strength;
(2) controlled rate of degradation;
(3) complete absorbability without the formation of toxic metabolites (hydrolytic byproducts are processed through the tricarboxylic acid cycle and eliminated as carbon dioxide via respiration); and
(4) minimal inflammatory response from the host. Many of these polymers, however, are severely lacking either in their initial strength or their rate of degradation. Only the polyesters polydioxanone (PDS), polyglycolic acid (PGA), and polylactic acid (PLA) possess adequate strength and a predictable degradation rate. Of these, copolymers of PGA and PLA have demonstrated an accelerated rate of osseous wound healing. Homopolymers of PLA and PGA and copolymers of PGA/PLA have been investigated for use as absorbable sutures, as implants to repair fractures of the orbital floor, as biodegradable plates for internal fixation of mandibular fractures, and as foam meshworks to facilitate healing extraction sockets. Both homopolymers of PGA and PLA as well as copolymers of PGA/PLA, produce only a minimal to slight inflammatory response in tissue. Degradation of PGA/PLA copolymers occurs by random hydrolytic cleavage of ester linkages in the chain and is independent of enzymatic activity. There is evidence that metabolites of copolymer degradation are processed through the Krebs cycle and eliminated as carbon dioxide through respiration. Copolymers of 25% PGA have been found to degrade fastest followed by 50% PLA:50% PGA, 75% PLA:24% PGA, and homopolymers of PLA and PGA, respectively. During the requisite period necessary for fracture fixation (4-10 weeks), 50PLA:50PGA will degrade roughly 50%, completing 100% dissolution in 120 days.
The mechanical properties of PGA/PLA copolymers have been found to vary depending on their percent composition and degree of crystallinity. DL-polylactide which is less crystalline than the L(-)-polylactide seems to be more succeptible to hydrolytic degradation. The DL-polylactide also has a problem with dimensional stability manifested as shrinkage following implantation.
From a morphological standpoint, the irregular, open-lattice type of texture visible on SEM photomicrographs makes the copolymer an ideal trestle to promote bony ingrowth as well as a carrier for other osteoinductive agents.